Journal
FEBS JOURNAL
Volume 274, Issue 16, Pages 4199-4210Publisher
WILEY
DOI: 10.1111/j.1742-4658.2007.05946.x
Keywords
CyaY; Friedreich's ataxia; iron binding; NMR; x-ray
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Funding
- MRC [MC_U117584256, MC_U117533887] Funding Source: UKRI
- Medical Research Council [MC_U117584256, MC_U117533887] Funding Source: researchfish
- Medical Research Council [MC_U117533887, MC_U117584256] Funding Source: Medline
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Deficiency of the small mitochondrial protein frataxin causes Friedreich's ataxia, a severe neurodegenerative pathology. Frataxin, which has been highly conserved throughout evolution, is thought to be involved in, among other processes, Fe-S cluster formation. Independent evidence shows that it binds iron directly, although with very distinct features and low affinity. Here, we have carried out an extensive study of the binding properties of CyaY, the bacterial ortholog of frataxin, to different divalent and trivalent cations, using NMR and X-ray crystallography. We demonstrate that the protein has low cation specificity and contains multiple binding sites able to chelate divalent and trivalent metals with low affinity. Binding does not involve cavities or pockets, but exposed glutamates and aspartates, which are residues that are unusual for iron chelation when not assisted by histidines and/or cysteines. We have related how such an ability to bind cations on a relatively large area through an electrostatic mechanism could be a valuable asset for protein function.
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